Phosphorylation of histone H3Ser10 in plant cell division

Histones, the major protein components of chromatin, undergo post-translational modifications, which particularly affect the structural and functional organization of chromosomes. The most common post-translational modifications are phosphorylation, methylation, acetylation and ubiquitination. Histone phosphorylation occurs mainly at N-terminal tails of serines (Ser) and threonines (Thr), and coordinates various processes of mitotic and meiotic division. It has been shown that this type of modification is required for activation of transcription, DNA damage repair, recombination and also for chromosome condensation and segregation. Histone H3 is characterised by the presence of a large number of modification sites among the four core histones. In plants, phosphorylation of histone H3 at serine positions 10 and 28 and at threonine positions 3, 11, 32 and 133 is the most well studied. This review contains the most complete data on the spatial and temporal distribution of H3 phosphorylation of serine at position 10 (phH3Ser10) in mitosis and meiosis in different plant species. Most species are characterised by phosphorylation of the centromeric region in mitosis and second meiotic division, and by phosphorylation throughout the chromosomes in the first meiotic division. However, there are exceptions to the phH3Ser10 distribution in mosses and cestrum, as well as in species with holocentric chromosomes. There are contradictory data on the phH3Ser10 distribution in mitosis and meiosis in the same species. The functional significance of phH3Ser10 in cell division in plants is associated with the activity of the centromere, centromere cohesion and sister chromatid and chromosome segregation. We discuss the participation of currently known candidate kinases and phosphatases in the dynamics of H3Ser10 phosphorylation. The review provides an overview of the role of phH3Ser10 modification in the chromosome division and segregation in mitosis and meiosis

Electronic and Geometric Corrugation of Periodically Rippled, Self-nanostructured Graphene Epitaxially Grown on Ru(0001)

Graphene epitaxially grown on Ru(0001) displays a remarkably ordered pattern of hills and valleys in Scanning Tunneling Microscopy (STM) images. To which extent the observed "ripples" are structural or electronic in origin have been much disputed recently. A combination of ultrahigh resolution STM images and Helium Atom diffraction data shows that i) the graphene lattice is rotated with respect to the lattice of Ru and ii) the structural corrugation as determined from He diffraction is substantially smaller (0.015 nm) than predicted (0.15 nm) or reported from X-Ray Diffraction or Low Energy Electron Diffraction. The electronic corrugation, on the contrary, is strong enough to invert the contrast between hills and valleys above +2.6 V as new, spatially localized electronic states enter the energy window of the STM. The large electronic corrugation results in a nanostructured periodic landscape of electron and holes pockets.Comment: 16 pages, 6 figure

In situ observation of stress relaxation in epitaxial graphene

Upon cooling, branched line defects develop in epitaxial graphene grown at high temperature on Pt(111) and Ir(111). Using atomically resolved scanning tunneling microscopy we demonstrate that these defects are wrinkles in the graphene layer, i.e. stripes of partially delaminated graphene. With low energy electron microscopy (LEEM) we investigate the wrinkling phenomenon in situ. Upon temperature cycling we observe hysteresis in the appearance and disappearance of the wrinkles. Simultaneously with wrinkle formation a change in bright field imaging intensity of adjacent areas and a shift in the moire spot positions for micro diffraction of such areas takes place. The stress relieved by wrinkle formation results from the mismatch in thermal expansion coefficients of graphene and the substrate. A simple one-dimensional model taking into account the energies related to strain, delamination and bending of graphene is in qualitative agreement with our observations.Comment: Supplementary information: S1: Photo electron emission microscopy and LEEM measurements of rotational domains, STM data of a delaminated bulge around a dislocation. S2: Movie with increasing brightness upon wrinkle formation as in figure 4. v2: Major revision including new experimental dat

The creation and characterization of the bread wheat line with a centric translocation T2DL.2RL

The development of bread wheat introgressions with alien genetic material from cultural and wild Triticeae species is an effective method for expanding the wheat gene pool necessary for breeding. To date, numerous collections of introgressions as substitutions and chromosome modifications have been obtained; however, the creation and study of wheat with new valuable traits still remain an important line of research. Rye Secale cereale L., whose chromosomes carry genes that control valuable economic and biological characteristics and properties, is widely used to produce new wheat forms. In this study, a wheat-rye translocation obtained by backcrossing the wheat-rye disomic-substitution line 2R(2D)1 with the variety Novosibirskaya 67 was characterized. The chromosomal composition of karyotypes was studied using fluorescent in situ hybridization and C-banding. Two centric translocations, derived from two long arms of chromosomes 2D and 2R, T2DL.2RL, were identified, the remaining 40 wheat chromosomes did not undergo modifications. Meiosis in the lines was stable. Chromosomes T2DL.2RL formed bivalents in all meiocytes, which confirmed their homology. The morphological characteristics of the spike in the T2DL.2RL line and Novosibirskaya 67 did not differ. A comparative analysis of productivity between the T2DL.2RL translocation line and the parental forms, Novosibirskaya 67 and the 2R(2D)1 line, was carried out. The T2DL.2RL line is inferior to Novosibirskaya 67 in all characters with different confidence levels. The productivity characters of the 2R(2D)1 line exceeded or did not differ from those of T2DL.2RL, however, the mass of 1000 grains was significantly lower. The results showed the effect of the T2DL.2RL translocation on the trait “plant height”. This character was significantly lower than that of Novosibirskaya 67 in two vegetation periods. Consequently, the T2DL.2RL translocation reduces plant height and productivity

Prevalence of the most frequent BRCA1 mutations in Polish population

The purpose of our study was to establish the frequency and distribution of the four most common BRCA1 mutations in Polish general population and in a series of breast cancer patients. Analysis of the population frequency of 5382insC (c.5266dupC), 300T >G (p.181T >G), 185delAG (c.68_69delAG) and 3819del5 (c.3700_3704del5) mutations of the BRCA1 gene were performed on a group of respectively 16,849, 13,462, 12,485 and 3923 anonymous samples collected at birth in seven Polish provinces. The patient group consisted of 1845 consecutive female breast cancer cases. The most frequent BRCA1 mutation in the general population was 5382insC found in 29 out of 16,849 samples (0.17%). 300T >G and 3819del5 mutations were found in respectively 11 of 13,462 (0.08%) and four of 3923 (0.1%) samples. The population prevalence for combined Polish founder 5382insC and 300T >G mutations was 0.25% (1/400). The frequencies of 5382insC and 300T >G carriers among consecutive breast cancer cases were, respectively, 1.9% (35/1845) and 1.2% (18/1486). Comparing these data with the population frequency, we calculated the relative risk of breast cancer for 5382insC mutation at OR = 17 and for 300T >G mutation at OR = 26. Our results, based on large population studies, show high frequencies of founder 5382insC and 300T >G BRCA1 mutations in Polish general population. Carriage of one of these mutations is connected with a very high relative risk of breast cancer

Тонкая кишка в остром периоде спинальной травмы: ранние нарушения метаболизма по данным флуоресцентного время-разрешенного имиджинга FLIM

RELEVANCE A special place in the development of enteral insufficiency is given to dysproteinemia, which is one of the leading causes of the development of decubital ulcers in patients with spinal cord injury. Early enteral nutrition partially solved this problem, but the incidence of bedsores still remains high and reaches 68%. The risk of metabolic disorders in the acute period of spinal injury is largely determined by non-occlusive intestinal ischemia against the background of spinal shock, neurohumoral dysregulation; intra-intestinal and intra-abdominal hypertension; change in intestinal microflora. Pathological changes in the intestinal wall occur during the first 20 days after injury and further exacerbate chronic maldigestion, malabsorption, intestinal dyskinesia in patients with traumatic spinal cord disease. New knowledge about the features of early enteral nutrition in patients in the acute period of traumatic spinal cord disease will reduce the risk of decubitus ulcerative defects.AIM OF THE STUDY To study the dynamics of metabolic processes in the tissues of the small intestine in the acute period of spinal injury.MATERIAL AND METHODS Wistar rats (n=22). Spinal injury was simulated by acute complete transection of the spinal cord at the level of Th5–Th6 vertebrae. The assessment of metabolic changes in the cells of the serous membrane of the intestine was performed immediately, 3 and 24 hours after injury. The metabolism was assessed in vivo using fluorescence time-resolved macroimaging technology FLIM by autofluorescence in the spectral channel of the metabolic cofactor nicotinamide adenine dinucleotide (phosphate).RESULTS The acute period of spinal cord injury is accompanied by a change in the endogenous autofluorescence of the serous membrane of the small intestine: a statistically significant decrease in the mean fluorescence lifetime (τm), the lifetime of the long component (τ2), and the relative contribution of the long component (а2) in 24 h after injury was recorded. The changes observed using FLIM confirm the catabolic type of metabolism in the tissues of the small intestine after spinal cord injury.CONCLUSION For the first time in the experiment in vivo it has been shown that the acute period of spinal injury is accompanied by a violation of metabolic processes in the tissues of the small intestine. This fact requires a more balanced approach in calculating the calorie content of nutrients used for early enteral nutrition in patients with spinal cord injury.АКТУАЛЬНОСТЬ Особое место в развитии энтеральной недостаточности отводится диспротеинемии, которая является одной из ведущих причин развития декубитальных язв у пациентов с травмой спинного мозга. Раннее энтеральное питание частично решило указанную проблему, однако частота развития пролежней по-прежнему остается на высоком уровне и достигает 68%. Риск нарушения метаболизма в остром периоде спинальной травмы во многом определяется неокклюзивной ишемией кишечника на фоне спинального шока, нейрогуморальной дисрегуляции; внутрикишечной и внутрибрюшной гипертензией; сменой кишечной микрофлоры. Патоморфологические изменения в стенке кишки происходят в течение первых 20 суток после травмы и в дальнейшем усугубляют хронические мальдигестию, мальабсорбцию, кишечную дискинезию у пациентов с травматической болезнью спинного мозга. Новые знания относительно особенностей раннего энтерального питания пациентов в остром периоде травматической болезни спинного мозга позволят сократить риск формирования декубитальных язвенных дефектов.ЦЕЛЬ ИССЛЕДОВАНИЯ Изучить динамику метаболических процессов в тканях тонкой кишки в остром периоде спинальной травмы.МАТЕРИАЛ И МЕТОДЫ Эксперимент проводился на лабораторных животных — крысах линии Wistar (n=22). Спинальную травму моделировали острым полным пересечением спинного мозга на уровне Th5–Th6 позвонков. Оценку метаболических изменений в клетках серозной оболочки кишечника проводили сразу, через 3 и через 24 часа после травмы. Метаболизм оценивали in vivo с помощью технологии флуоресцентного время-разрешенного макроимиджинга FLIM по автофлуоресценции в спект­ральном канале метаболического кофактора никотинамидадениндинуклеотида (фосфат).РЕЗУЛЬТАТЫ Острый период травмы спинного мозга сопровождается изменением эндогенной автофлуоресценции тканей серозной оболочки тонкой кишки: зафиксировано статистически значимое снижение среднего времени жизни флуоресценции (τm), времени жизни длинной компоненты (τ2) и процентного вклада длинной компоненты (а2) затухания через 24 часа после травмы. Наблюдаемые с помощью FLIM изменения подтверждают катаболическую направленность обмена веществ в тканях тонкой кишки после травмы спинного мозга.ЗАКЛЮЧЕНИЕ Впервые в эксперименте in vivo показано, что острый период спинальной травмы сопровождается нарушением метаболических процессов в тканях тонкой кишки. Данный факт требует более взвешенного подхода в расчете калорийности питательных веществ, используемых для раннего энтерального питания пациентов с травмой спинного мозга

Раннее назначение генно-инженерных биологических препаратов при иммуновоспалительных заболеваниях: возможности и перспективы. Позиция экспертов

Psoriasis (Ps), psoriatic arthritis (PsA), and inflammatory bowel diseases (IBDs) are characterized by a progressive course and frequently lead to disability; therefore, their early diagnosis with the assessment of a clinical phenotype and unfavorable prognostic factors and the timely initiation of therapy are important tasks. The paper provides the experts agreed opinion on the definition of the early stage of Ps, PsA, and IBDs, the goals of therapy and main unfavorable prognostic factors for the course of these diseases and gives the rationale for the early use of biological agents in patients with immune-mediated inflammatory diseases.Псориаз (Пс), псориатический артрит (ПсА) и воспалительные заболевания кишечника (ВЗК) характеризуются прогрессирующим течением и нередко приводят к инвалидизации, поэтому важными задачами являются их ранняя диагностика с оценкой клинического фенотипа и факторов неблагоприятного прогноза и своевременное начало терапии. В статье приводятся согласованная позиция экспертов по определению ранней стадии Пс, ПсА и ВЗК, цели терапии и основные факторы неблагоприятного прогноза течения этих заболеваний, представлено обоснование раннего применения генно-инженерных биологических препаратов у пациентов с иммуновоспалительной патологией

Modeling morphological instabilities in lipid membranes with anchored amphiphilic polymers

Anchoring molecules, like amphiphilic polymers, are able to dynamically regulate membrane morphology. Such molecules insert their hydrophobic groups into the bilayer, generating a local membrane curvature. In order to minimize the elastic energy penalty, a dynamic shape instability may occur, as in the case of the curvature-driven pearling instability or the polymer-induced tubulation of lipid vesicles. We review recent works on modeling of such instabilities by means of a mesoscopic dynamic model of the phase-field kind, which take into account the bending energy of lipid bilayers

Результаты неинтервенционного наблюдательного многоцентрового исследования тактики ведения пациентов с аксиальным псориатическим артритом в условиях реальной клинической практики (NiSaXPA)

Psoriatic arthritis (PsA) is a chronic immunoinflammatory disease of the joints, spine and entheses from the group of spondyloarthritis, which is usually observed in patients with psoriasis. In recent years, the axial form of PsA (axPsA) has been actively researched. However, there is insufficient data on approaches to the diagnosis and treatment of patients with axPsA in real-life clinical practice. This article presents the results of an interim analysis of data from a non-interventional multicenter observational study on the treatment of patients with axPsA in real-life clinical practice (NiSaXPA) in Russian centers.Objective: to identify patients with axPsA, their characteristics and describe treatment tactics in real-life clinical practice.Material and methods. Patients with PsA who met the inclusion criteria were prospectively followed up during routine visits to a rheumatologist. Participants' axial radiographs were uploaded to a database in order for it to be confirmed the presence or absence of axPsA by two independent experts, a rheumatologist and a radiologist. Patients with a confirmed axPsA diagnosis participated in a further data collection phase (Visit 2, week 24).Results and discussion. Six hundred patients were enrolled into the study. At the time of analysis, 386 (64.3%) of them (209 men and 177 women) were screened for axPsA. The diagnosis of axPsA was confirmed in 241 (62.4%) cases; these patients formed the Per Protocol (PP) population. The mean age of patients with axPsA in the PP population was 46.30±12.6 years and the body mass index (BMI) was 27.4±5.2 kg/m2 . In 14.9% of patients, the duration of psoriasis was less than 1–5 years, in 21.5% – 5–10 years and in 63.6% – more than 10 years. The duration of PsA symptoms was less than 1–5 years in 31.2 % of patients, 5–10 years in 31.6 % and more than 10 years in 37.2 %. Low disease activity (BASDAI ˂ 4) was achieved in 33.3 % of patients with axPsA at visit 1 and in 64.3 % at visit 2; the BASDAI index declined on average from 4.67±1.95 to 3.31±1.89 points.In real-life clinical practice, patients were most frequently prescribed non-steroidal anti-inflammatory drugs (NSAIDs) – 88.7% and 71.7% (visits 1 and 2, respectively), and synthetic disease-modifying antirheumatic drugs (sDMARDs) –79.1% and 70.7%, respectively; therapy with biologic disease-modifying antirheumatic drugs (bDMARDs) was initiated in 40.2% and 60.6% of patients, respectively.Conclusion. The results of the interim analysis of this observational study showed that in 87.2% of patients who met the CASPAR criteria for PsA there was a suspicion of axial manifestations of PsA on the primary care level. However, only 62.4% of them had a confirmed diagnosis of axPsA on centralized expert assessment, which may indicate a possible overdiagnosis of axial lesions in real-life practice and emphasizes the importance of collaboration between a rheumatologist and a radiologist when analyzing the results of imaging studies. 33.3% of patients with axPsA had low disease activity according to BASDAI at baseline and 64.3% after 24 weeks, meaning that the disease was only adequately controlled in one third of cases despite therapy; the number of these patients doubled after a change in therapy. In real-world clinical practice, patients with axPsA are most commonly prescribed drugs from the NSAID and sDMARD groups; the frequency of use of biologic drugs varied between 40.2 and 60.6% by the end of the observation period.Псориатический артрит (ПсА) – хроническое иммуновоспалительное заболевание суставов, позвоночника и энтезисов из группы спондилоартритов, которое обычно наблюдается у больных псориазом. В последние годы активно изучается аксиальная форма ПсА (аксПсА). Вместе с тем данных о подходах к диагностике и ведению пациентов с аксПсА в реальной клинической практике недостаточно. В настоящей публикации представлены результаты промежуточного анализа данных неинтервенционного наблюдательного многоцентрового исследования тактики ведения пациентов с аксПсА в условиях реальной клинической практики (NiSaXPA) в российских центрах.Цель исследования – выявление пациентов с аксПсА, их характеристика и описание тактики ведения в условиях реальной клинической практики.Материал и методы. Во время плановых визитов к ревматологу проводилось проспективное наблюдение пациентов с ПсА, соответствовавших критериям включения. Аксиальные рентгенограммы участников были загружены в базу данных для подтверждения наличия или отсутствия аксПсА двумя независимыми экспертами – ревматологом и рентгенологом. Пациенты с подтвержденным диагнозом аксПсА участвовали в дальнейшей фазе сбора данных (визит 2, неделя 24).Результаты и обсуждение. В исследование включено 600 пациентов. На момент проведения анализа с целью выявления аксПсА обследовано 386 (64,3%) из них (209 мужчин и 177 женщин). Диагноз аксПсА подтвержден в 241 (62,4%) случае; эти больные составили популяцию по протоколу (PP, Per Protocol). У 145 (37,6%) пациентов аксПсА не выявлен. Возраст пациентов с аксПсА в популяции РР составил в среднем 46,30±12,6 года, индекс массы тела (ИМТ) – 27,4±5,2 кг/м2 . У 14,9% пациентов длительность псориаза была менее 1–5 лет, у 21,5% – 5–10 лет и у 63,6% – более 10 лет. Давность симптомов ПсА у 31,2% пациентов составляла менее 1–5 лет, у 31,6% – 5–10 лет и у 37,2% – более 10 лет. Низкой активности заболевания (BASDAI ˂ 4) к визиту 1 достигли 33,3% больных аксПсА, к визиту 2 – 64,3%; было отмечено снижение индекса BASDAI в среднем с 4,67±1,95 до 3,31±1,89 балла. В реальной клинической практике пациентам наиболее часто назначали нестероидные противовоспалительные препараты (НПВП) – 88,7% и 71,7% (визиты 1 и 2 соответственно) и синтетические базисные противовоспалительные препараты (сБПВП) – 79,1% и 70,7% соответственно; терапия генно-инженерными биологическими препаратами (ГИБП) была инициирована 40,2% и 60,6% больных соответственно.Заключение. Результаты промежуточной оценки данного наблюдательного исследования показали, что у 87,2% пациентов, отвечавших критериям CASPAR для ПсА, исходно при обследовании по месту жительства были заподозрены аксиальные проявления ПсА. Однако при центральной экспертной оценке диагноз аксПсА был верифицирован только у 62,4% из них, что может свидетельствовать о возможной гипердиагностике аксиального поражения в реальной практике и подчеркивает важность кооперации ревматолога и рентгенолога при анализе результатов визуализационных методов обследования. 33,3% пациентов с аксПсА имели низкую активность заболевания по BASDAI исходно и 64,3% – через 24 нед. Таким образом, несмотря на проводимую терапию, адекватно контролировать заболевание удавалось только в трети случаев, после смены терапии число таких пациентов увеличилось вдвое. В реальной клинической практике пациентам с аксПсА наиболее часто назначают препараты из группы НПВП и сБПВП, частота использования ГИБП варьировалась от 40,2 до 60,6% к концу наблюдения